Microdroplets show great promise as a new high-throughput technology in chemistry, biochemistry and molecular biology. Microdroplets can be generated at rates in excess of several thousands per second and accurately formulated using minute amounts of small molecules, DNA, proteins or cells. Furthermore, integrated active elements can be used to control individual microdroplets. Technology for creating, dividing, fusing, interrogating and even sorting microdroplets has already been developed.
Microdroplets are naturally self-contained microreactors that generally reduce sample loss, diffusion and cross-contamination, general issues that afflict traditional microfluidics. However, the isolated nature of microdroplets impedes physical access to their contents. Moreover, while analytical techniques such as mass spectrometry, capillary electrophoresis or liquid chromatography have been integrated with continuous flow microfluidic devices, their integration with microdroplets remains hindered.
There therefore remains a need for improved techniques for processing microdroplets such as, inter alia, to improve detection of microdroplet contents. More specifically regarding detection of an analyte or mixture of analytes in one or more microdroplets, improvements are needed such as label-independent analyte detection, faster analyte detection, increased detection sensitivity, e.g. by detection with reduced noise and/or contamination, for example to achieve a reduced minimum concentration of analyte in microdroplet that can be detected, etc. Further processing advantages may be found for example in improving flow of microdroplets containing analyte.
There are many prior art documents describing in general terms the integration of ESI-MS with microfluidic devices.
For use in understanding the present invention, we refer to the following disclosures:                International patent application publication WO2007/136386 A2, published Nov. 29, 2007, The Regents of the University of California, inventors Wheeler, Garrell et al.;        US patent application publication US2010/0018864 A1, published Jan. 28, 2010, Commisariat A L'Energie Atomique, inventors Sarrut and Constantin;        US patent application publication US2005/0178960 A1, published Aug. 18, 2005, Cornell Research Foundation Inc., inventors Kameoka, Craighead;        Holt, D., et al., “Fluorosurfactants for microdroplets: Interfacial tension analysis, Journal of Colloid and Interface Science, 2010, Vol. 350(1), pp 205-211,        Holt, D., et al., “Synthesis of novel fluorous surfactants for microdroplet stabilisation in fluorous oil streams”, Journal of Fluorine chemistry, 2009, Vol. 131(3), pp 398-407;        “Coupling microdroplet microreactors with mass spectrometry: reading the contents of single microdroplets online”, Angew Chem Int Ed Engl. 2009; 48(20):3665-8, Published Online: 7 Apr. 2009, Fidalgo L M, Whyte G, Ruotolo B T, Benesch J L, Stengel F, Abell C, Robinson C V, Huck W T;        “Analysis of Samples Stored as Individual Plugs in a Capillary by Electrospray Ionization Mass Spectrometry”, Anal. Chem., 2009, 81 (15), pp 6558-6561, publication date (web): Jun. 25, 2009, Jian Pei, Qiang Li, Mike S. Lee, Gary A. Valaskovic and Robert T. Kennedy;        “Dilution-free analysis from picoliter microdroplets by nano-electrospray ionization mass spectrometry”, Angew Chem Int Ed Engl. 2009; 48(37):6832-5, published Online: 17 Aug. 2009 Kelly R T, Page J S, Marginean I, Tang K, Smith R D;        C. Holtze, A. C. Rowat, J. J. Agresti, J. B. Hutchison, F. E. Angilè, C. H. J. Schmitz, S. Koster, H. Duan, K. J. Humphry, R. A. Scanga, J. S. Johnson, D. Pisignano and D. A. Weitz, “Biocompatible surfactants for water-in-fluorocarbon emulsions”, Lab Chip, 2008, 8, 1632-1639; and        US patent application publication US2008/0067343 A1, published Mar. 20, 2008, Hirota et al.        
Other background art is found in the following patent documents:                US 2010/0018864A1 Lab-on-a-chip with coplanar microfluidic network and coplanar electrospray nozzle, Jan. 28, 2010;        US 2008/0235948A1 Electrospray apparatus with an integrated electrode, Oct. 2, 2008;        GB 2437844A, Microfluidic device for electrospraying, Nov. 7, 2007;        US 2007/0128078A1 Lab-on-a-chip comprising a coplanar microfluidic system and electrospray nozzle, Jun. 7, 2007;        US 2007/0114385A1 Microfluidic device comprising an electrospray nose, May 24, 2007;        US 2006/0193748A1, Integrated LC-ESI on a chip, Aug. 31, 2006;        US 2006/0022130A1 Microfluidic devices and methods with integrated electrical contact, Feb. 2, 2006;        US 2005/0178960A1, Electrospray emitter for microfluidic channel, Aug. 18, 2005;        WO 2005/019804A2 Microfluidic chip with enhanced tip for stable electrospray ionisation, 3 Mar. 2005;        US 2004/0229377A1, Microfluidic chip system integrated with nano-electrospray interface and method using thereof, Nov. 18, 2004;        EP 1465230A2, Electrospray emitter for microfluidic channel, Oct. 6, 2004;        US 2003/0211631A1, Microfluidic devices connected to capillaries with minimal dead volume, Nov. 13, 2003;        US 2003/0026740A1, Microfluidic devices, Feb. 6, 2003;        WO2008/021123.        